Genetic Variant OXCT1:c.-133G>A (chr5-41870491-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000972071.1(OXCT1):c.-133G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000056 in 713,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000053 ( 0 hom. )

Consequence

OXCT1
ENST00000972071.1 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0120

Publications

0 publications found

Variant links:

Genes affected

OXCT1 (HGNC:8527): (3-oxoacid CoA-transferase 1) This gene encodes a member of the 3-oxoacid CoA-transferase gene family. The encoded protein is a homodimeric mitochondrial matrix enzyme that plays a central role in extrahepatic ketone body catabolism by catalyzing the reversible transfer of coenzyme A from succinyl-CoA to acetoacetate. Mutations in this gene are associated with succinyl CoA:3-oxoacid CoA transferase deficiency. [provided by RefSeq, Jul 2008]

OXCT1 links:

OXCT1-AS1 (HGNC:40423): (OXCT1 antisense RNA 1)

OXCT1-AS1 links:

LOC102723752 (HGNC:):

LOC102723752 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000972071.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
OXCT1-AS1	NR_046635.1		n.255+109C>T	intron	N/A
OXCT1	NM_000436.4	MANE Select	c.-133G>A	upstream_gene	N/A	NP_000427.1	P55809-1
OXCT1	NM_001364299.2		c.-133G>A	upstream_gene	N/A	NP_001351228.1

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
OXCT1	ENST00000972071.1	c.-133G>A	5_prime_UTR	Exon 1 of 18	ENSP00000642130.1
OXCT1	ENST00000972069.1	c.-133G>A	5_prime_UTR	Exon 1 of 16	ENSP00000642128.1
OXCT1	ENST00000899738.1	c.-133G>A	5_prime_UTR	Exon 1 of 16	ENSP00000569797.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000534

AC:

AN:

561620

Hom.:

Cov.:

AF XY:

0.00000663

AC XY:

AN XY:

301656

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15680

American (AMR)

AF:

0.00

AC:

AN:

33666

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19368

East Asian (EAS)

AF:

0.00

AC:

AN:

31908

South Asian (SAS)

AF:

0.00

AC:

AN:

61292

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33534

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2426

European-Non Finnish (NFE)

AF:

0.00000900

AC:

AN:

333356

Other (OTH)

AF:

0.00

AC:

AN:

30390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Succinyl-CoA acetoacetate transferase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.6

(source)

DANN

Benign

0.75

PhyloP100

0.012

PromoterAI

-0.099

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over